Inhibition of nitric oxide synthase increases synaptophysin mRNA expression in the hippocampal formation of rats.

Synaptophysin is a protein involved in the biogenesis of synaptic vesicles and budding. It has been used as an important tool to investigate plastic effects on synaptic transmission. Nitric oxide (NO) can influence plastic changes in specific brain regions related to cognition and emotion. Experimental evidence suggests that NO and synaptophysin are co-localized in several brain regions and that NO may change synaptophysin expression. Therefore, the aim of the present work was to investigate if inhibition of NO formation would change synaptophysin mRNA expression in the hippocampal formation. Male Wistar rats received single or repeated (once a day for 4 days) i.p. injections of saline or l-nitro-arginine (l-NOARG, 40mg/kg), a non-selective inhibitor of nitric oxide synthase (NOS). Twenty-four hours after the last injection the animals were sacrificed and their brains removed for 'in situ' hybridization study using (35)S-labeled oligonucleotide probe complementary to synaptophysin mRNA. The results were analyzed by computerized densitometry. Acute administration of l-NOARG induced a significant (p<0.05, ANOVA) increase in synaptophysin mRNA expression in the dentate gyrus, CA1 and CA3. The effect disappeared after repeated drug administration. No change was found in the striatum, cingulated cortex, substantia nigra or nucleus accumbens. These results reinforce the proposal that nitric oxide is involved in plastic events in the hippocampus.